RM2Target: a comprehensive database for targets of writers, erasers and readers of RNA modifications

Abstract

RNA modification is a dynamic and reversible process regulated by a series of writers, erasers and readers (WERs). Abnormal changes of WERs will disrupt the RNA modification homeostasis of their target genes, leading to the dysregulation of RNA metabolisms such as RNA stability and translation, and consequently to diseases such as cancer. A public repository hosting the regulatory relationships between WERs and their target genes will help in understanding the roles of RNA modifications in various physiological and pathological conditions. Previously, we developed a database named ‘m6A2Target’ to host targets of WERs in m6A, one of the most prevalent RNA modifications in eukaryotic cells. To host all RNA modification (RM)-related WER–target associations, we hereby present an updated database, named ‘RM2Target’ (http://rm2target.canceromics.org/). In this update, RM2Target encompasses 1 619 653 WER–target associations for nine RNA modifications in human and mouse, including m6A, m6Am, m5C, m5U, m1A, m7G, pseudouridine, 2′-O-Me and A-to-I. Extensive annotations of target genes are available in RM2Target, including but not limited to basic gene information, RNA modifications, RNA–RNA/RNA–protein interactions and related diseases. Altogether, we expect that RM2Target will facilitate further downstream functional and mechanistic studies in the field of RNA modification research.

LRPPRC facilitates tumor progression and immune evasion through upregulation of m6A modification of PD-L1 mRNA in hepatocellular carcinoma

“…We firstly used the RM2Target platform ( http://rm2target.canceromics.org/ ) to predict the m 6 A modification role of LRPPRC in PD-L1 ( 23 ). Our prediction data demonstrated that PD-L1 might be potentially modified by LRPPRC-mediated m 6 A modification.…”

Dynamic regulation and key roles of ribonucleic acid methylation

“…The following are the emerged databases of methylation modifications associated with some specific diseases and fields: (1) After m6A methylation-related genes based on The Cancer Genome Atlas (TCGA) were used to predict the prognosis of hepatocellular carcinoma ( Group et al, 2020 ; Liu et al, 2020b ; Li et al, 2021b ), cancer-related methylation modification databases have begun to emerge, including, Lnc2Cancer 3.0 and OncoDB ( Gao et al, 2021 ; Tang et al, 2022 ); (2) Osteoarthritis-omics and molecular biomarkers (OAOB), which are a group of database containing differential molecular biomarkers related to osteoarthritis ( Li et al, 2022a ); (3) Other than disease, Pan et al (2022) established an integrative multi-omic database (iMOMdb) of Asian pregnant women providing the first blood-based multi-omic analysis of pregnant women in Asia. This database contains high-resolution genotypes, DNA methylation, and transcriptome profiles, and fills the knowledge gap of complex traits in populations of Asian ancestry; (4) Gao et al (2022) developed AgingBank, an experimentally supported multiomics database of information related to aging in multiple species; (5) ProMetheusDB, a database generated by analyzing and sorting cell culture experiments data using ML tools from the protein perspective ( Massignani et al, 2022 ); (6) compendium of protein lysine modifications (CPLM 4.0), a post-translational modification (PTMs) database ( Zhang et al, 2022 ); (7) tRNA-related databases containing high-throughput tRNA sequencing data ( Sajek et al, 2020 ); (8) RNAWRE and RM2 Target are two databases focusing on information of writers, readers, and erasers ( Nie et al, 2020 ; Bao et al, 2022 ); and (9) SyStemCell, a multiple-levels experimental database for stem cell research ( Yu et al, 2012 ). With the emergence of these specialized and multi-angle RNA methylation related databases, the traditional databases are also constantly updated and developed.…”

“…• RMDisease V2.0 (Song et al, 2022b), AgingBank (Gao et al, 2022), CPLM 4.0 (Zhang et al, 2022), OncoDB (Tang et al, 2022), ASMdb (Zhou et al, 2022), iMOMdb (Pan et al, 2022), OAOB (Li et al, 2022a), ProMetheusDB (Massignani et al, 2022), RM2Target (Bao et al, 2022(Bao et al, ) (2022 performance based on its SpinalNet architecture that was inspired by the human somatosensory system.…”

“…(5) ProMetheusDB, a database generated by analyzing and sorting cell culture experiments data using ML tools from the protein perspective (Massignani et al, 2022); (6) compendium of protein lysine modifications (CPLM 4.0), a post-translational modification (PTMs) database (Zhang et al, 2022); (7) tRNArelated databases containing high-throughput tRNA sequencing data (Sajek et al, 2020); (8) RNAWRE and RM2 Target are two databases focusing on information of writers, readers, and erasers (Nie et al, 2020;Bao et al, 2022); and (9) SyStemCell, a multiple-levels experimental database for stem cell research (Yu et al, 2012). With the emergence of these specialized and multi-angle RNA methylation related databases, the traditional databases are also constantly updated and developed.…”

The 2023 Nucleic Acids Research Database Issue and the online molecular biology database collection

“…tModBase ( 8 ) focuses on modifications of tRNA, their dynamics and biomedical implications, and the enzymes involved. RM2Target ( 9 ), a development of the earlier m6A2Target database ( 10 ), covers writes, erasers and readers of nine RNA modifications as well as diverse annotations and biomedical implications. The third of the trio, DirectRMDB ( 11 ), collects data from direct RNA sequencing that captures quantitative RNA modifications, annotating the results in an isoform-specific manner.…”